DOCSLIB.ORG

Interphotoreceptor Retinol-Binding Protein Ameliorates Diabetes-Induced Retinal Dysfunction and Neurodegeneration Through Rhodopsin

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Interphotoreceptor Retinol-Binding Protein Ameliorates Diabetes-Induced Retinal Dysfunction and Neurodegeneration Through Rhodopsin 788 Diabetes Volume 70, March 2021 Interphotoreceptor Retinol-Binding Protein Ameliorates Diabetes-Induced Retinal Dysfunction and Neurodegeneration Through Rhodopsin Jianglei Chen,1 Yan Shao,1,2 Temmy Sasore,1 Gennadiy Moiseyev,1 Kelu Zhou,1 Xiang Ma,1 Yanhong Du,1 and Jian-xing Ma1,3 Diabetes 2021;70:788–799 | https://doi.org/10.2337/db20-0609 Patients with diabetes often experience visual defects to a 2017 report by the International Diabetic Federation, before any retinal pathologies are detected. The molec- the worldwide prevalence of diabetes mellitus (DM) is 1 in ular mechanism for the visual defects in early diabetes 11 adults (425 million), and the number is skyrocketing has not been elucidated. Our previous study reported accompanying the economic growth and increasing life that in early diabetic retinopathy (DR), rhodopsin levels span in developing countries. were reduced due to impaired 11-cis-retinal regenera- DR was traditionally considered a microvascular com- tion. Interphotoreceptor retinol-binding protein (IRBP) is plication of diabetes, and pathological angiogenesis and cis a visual cycle protein and important for 11- -retinal vascular dysfunction were regarded as the priority in generation. IRBP levels are decreased in the vitreous and clinical treatment (2). Emerging evidence suggests that retina of DR patients and animal models. To determine the dysfunction of the retinal neurons and retinal neurode- role of IRBP downregulation in the visual defects in early DR, generation play important roles in the pathogenesis of DR we induced diabetes in transgenic mice overexpressing (3,4). Extensive reports have shown that oxidative stress, IRBP in the retina. IRBP overexpression prevented diabetes- characterized by overproduction of reactive oxygen species COMPLICATIONS induced decline of retinal function. Furthermore, IRBP over- expression also prevented decreases of rhodopsin levels (ROS), plays an important role in DR (5). ROS-induced fl and 11-cis-retinal generation in diabetic mice. Diabetic chronic in ammation can lead to retinal degeneration and IRBP transgenic mice also showed ameliorated retinal vascular injury in patients with diabetes (6). Anti-vascular oxidative stress, inflammation, apoptosis, and retinal de- endothelial growth factor drugs and laser photocoagula- generation compared with diabetic wild-type mice. These tion have been used to ameliorate retinal vascular pathol- findings suggest that diabetes-induced IRBP downregula- ogies in DR, especially in proliferative DR (7). Nevertheless, tion impairs the regeneration of 11-cis-retinal and rhodop- there is no effective treatment for retinal degeneration in sin, leading to retinal dysfunction in early DR. Furthermore, DR. increased 11-cis-retinal–free opsin constitutively activates Photoreceptors are the most abundant cells in the retina the phototransduction pathway, leading to increased oxi- and the most metabolically active neurons in the central dative stress and retinal neurodegeneration. Therefore, nervous system (8). Under diabetic conditions, increased restored IRBP expression in the diabetic retina may confer oxidative stress caused by mitochondrial dysfunction in a protective effect against retinal degeneration in DR. photoreceptor cells subsequently results in retinal inflam- mation, leading to vascular dysfunction (9). Interphotoreceptor retinol-binding protein (IRBP) was Diabetic retinopathy (DR) is the leading cause of vision loss first identified as a visual cycle protein, which is a retinol- and disability in the working-age population (1). According binding protein secreted from the photoreceptors and is 1Department of Physiology, University of Oklahoma Health Sciences Center, This article contains supplementary material online at https://doi.org/10.2337/ Oklahoma City, OK figshare.13363265. 2 Tianjin Medical University Eye Hospital, Eye Institute & School of Optometry and © 2020 by the American Diabetes Association. Readers may use this article as Ophthalmology, Tianjin, China long as the work is properly cited, the use is educational and not for profit, and the 3 Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, work is not altered. More information is available at https://www.diabetesjournals Oklahoma City, OK .org/content/license. Corresponding author: Jian-xing Ma, [email protected] Received 9 June 2020 and accepted 10 December 2020 diabetes.diabetesjournals.org Chen and Associates 789 present in the interphotoreceptor matrix of the retina For cone function, a series of flashes with 600 cd $ s/m2 (10). IRBP transports retinoids between the photorecep- intensity were applied to record the cone photoreceptor tors and the retinal pigment epithelium (RPE) (10,11) and response after 10-min light adaptation under a back- plays an important role in the regeneration of 11-cis- ground light of 50 cd/m2. ERG responses of both eyes retinal, the chromophore of visual pigments, and is thus were simultaneously recorded and analyzed. essential for maintaining normal visual function. IRBP also plays a role in retinal development (12,13) and shows Optical Coherence Tomography antioxidant activities via binding all-trans-retinal (14). The retinal thickness was measured using a spectral do- Recently, IRBP levels were reported to be decreased in the main optical coherence tomography (SD-OCT) device vitreous of DR patients, and IRBP conferred protective (Bioptigen, Durham, NC). Images were captured with the effects against DR in rodent models (15,16). rectangular scan at 1,000 A-scans per B scan, and 100 B- Rhodopsin regeneration and homeostasis are critical for scans per frame. Total retinal thickness was recorded and retinal function and health. The visual chromophore averaged automatically using the InVivoVue diver software 11-cis-retinal binds to opsin to form rhodopsin in the dark, (Bioptigen) by researchers blinded to the animal group which locks the opsin in an inactive state. Unbound free information. opsin is known to be constitutively active, which can exhaust photoreceptor cells and promote retinal degener- Immunohistochemistry and TUNEL of Eyecup Sections ation (17). In early diabetes, increased chromophore-free Mouse eyes were carefully enucleated and fixed in David- opsin due to insufficient 11-cis-retinal generation has been son’s fixation solution for 48 h The eyecups were paraffin suggested to have deleterious effects on photoreceptor embedded, and 5-mm sections were collected. The sections cells and accelerate DR progress (18). were immunostained with antibodies for 3-nitrotyrosine To identify the effect of diabetes-induced reduction of (3-NT) (ab61392; Abcam), glial fibrillary acidic protein IRBP on rhodopsin deficiency and retinal neurodegenera- (GFAP) (G-3893; Sigma-Aldrich), superoxide dismutase tion, we induced diabetes in transgenic mice overexpress- 2 (SOD2) (06-984; Millipore), NADPH oxidase 4 (NOX4) ing IRBP in photoreceptors. We assessed the role of IRBP (ab133303; Abcam), ionized calcium-binding adaptor mol- expression in diabetes-induced retinal function decline, ecule 1 (Iba1) (019-19741; Wako), arginase I (NBP1- retinal degeneration, and decreased 11-cis-retinal and 32731; Novus), and inducible nitric oxide synthase (iNOS) rhodopsin levels. The potential antioxidation and anti- (NBP1-97471; Novus) following the manufacturers’ pro- inflammation effects of IRBP on the diabetic retina were tocols. TUNEL staining was performed using the in situ further investigated. cell-death detection kit, TMRed (Roche Diagnostics, Indi- anapolis, IN) according to the manufacturer’s instruction. RESEARCH DESIGN AND METHODS Histological staining was performed on three sections per Animals animal, with five to six animals in each group of the same The animal experiments were conducted in compliance condition. Observation and imaging were performed under with the Association for Research in Vision and Ophthal- the same setting for each experiment using Olympus mology Statement for the Use of Animals in Ophthalmic FluoView (Version 2.1a) (Olympus, Tokyo, Japan). The and Vision Research. The protocol was approved by the images were analyzed and semiquantified with ImageJ University of Oklahoma Health Sciences Center Institu- (National Institutes of Health) by researchers blinded to tional Animal Care and Use Committee (Oklahoma City, the specimen identifications. OK). To induce diabetes, IRBP transgenic (IRBP-Tg) mice and Retinoid Profile Analysis wild-type (WT) littermates (12 weeks of age) received daily The retinoid profile was analyzed using high-performance intraperitoneal injections of streptozotocin (STZ; Sigma- liquid chromatography (HPLC), as described previously Aldrich) (55 mg/kg in 10 mmol/L of citrate buffer, pH 4.5) (18). Briefly, mice were sacrificed under dim red light after for five consecutive days. Blood glucose levels were mea- 16-h dark adaptation. The eyecup was homogenized in- sured 1 week after the last STZ injection and monthly dividually in lysis buffer (10 mmol/L NH2OH, 50% etha- thereafter. Animals with blood glucose levels .350 mg/dL nol, 50% 2-[N-morpholino] ethanesulfonic acid, pH 6.5), were defined as diabetic animals. and retinoids were extracted with hexane. The retinoids were dried under argon gas, resuspended in 200 mLof Electroretinography Recording mobile phase (11.2% ethyl acetate, 2.0% dioxane, 1.4% Scotopic electroretinography (ERG) and photopic ERG octanol, 85.4% hexane), and injected into HPLC (515 HPLC were both recorded monthly using the Diagnosys Espion pump; Waters, Milford, MA)
Load more

Recommended publications
  • Signaling by Sensory Receptors
    Signaling by Sensory Receptors David Julius1 and Jeremy Nathans2 1Department of Physiology, University of California School of Medicine, San Francisco, California 94158 2Department of Molecular Biology and Genetics, Johns Hopkins Medical School, Baltimore, Maryland 21205 Correspondence: [email protected] and [email protected] SUMMARY Sensory systems detect small molecules, mechanical perturbations, or radiation via the activa- tion of receptor proteins and downstream signaling cascades in specialized sensory cells. In vertebrates, the two principal categories of sensory receptors are ion channels, which mediate mechanosensation, thermosensation, and acid and salt taste; and G-protein-coupled recep- tors (GPCRs), which mediate vision, olfaction, and sweet, bitter, and umami tastes. GPCR- based signaling in rods and cones illustrates the fundamental principles of rapid activation and inactivation, signal amplification, and gain control. Channel-based sensory systems illus- trate the integration of diverse modulatory signals at the receptor, as seen in the thermosen- sory/pain system, and the rapid response kinetics that are possible with direct mechanical gating of a channel. Comparisons of sensory receptor gene sequences reveal numerous exam- ples in which gene duplication and sequence divergence have created novel sensory specific- ities. This is the evolutionary basis for the observed diversity in temperature- and ligand- dependent gating among thermosensory channels, spectral tuning among visual pigments, and odorant binding among olfactory receptors. The coding of complex external stimuli by a limited number of sensory receptor types has led to the evolution of modality-specific and species-specific patterns of retention or loss of sensory information, a filtering operation that selectively emphasizes features in the stimulus that enhance survival in a particular ecological niche.
    [Show full text]
  • Functional Analysis of Mammalian Cryptochromes a Matter of Time
    Functional Analysis of Mammalian Cryptochromes A Matter of Time The studies presented in this thesis were performed in the Department of Genetics, Chronobiology and Health Researcher Group at the Erasmus University Medical Centre in Rotterdam, The Netherlands. The Department is a member of the Medisch Genetisch Centrum Zuid-West Nederland (MGC). The research has been supported financially by NWO. Cover: Inspired by “Hommage à Apollinaire” Marc Chagall, 1911-1912, Collection Van Abbemuseum in Eindhoven, The Netherlands. Layout: Dan G.M. Vennix Printer: Wöhrman Print Service, Zutphen Functional Analysis of Mammalian Cryptochromes A Matter of Time Functionele analyse van zoogdier cryptochromen Een kwestie van tijd proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof.dr. H.G. Schmidt en volgens besluit van het College voor Pro moties De openbare verdediging zal plaatsvinden op woensdag 4 november 2009 om 9:30 uur door ͂ Monika Iwona Bajek geboren te Stalowa Wola, Polen Promotiecommissie Promotors Prof.dr. G.T.J. van der Horst Prof.dr. J.H.J. Hoeijmakers Overige leden Prof.dr. F.G. Grosveld Prof.dr. J.H. Meijer Prof.dr. B.A. Oostra ....... dla Frania i naszego Aniołka Marysi 7 Contents Chapter 1 Introduction 11 I The circadian clock 13 Historical background 13 Circadian oscillator mechanisms 15 Master clock – suprachiasmatic nucleus 17 Photoentrainment 19 Peripheral clock 20 II The photolyase/cryptochrome flavoprotein family 21 Photolyase 22 Structural analysis of
    [Show full text]
  • The UV-B Photoreceptor UVR8: from Structure to Physiology
    The Plant Cell, Vol. 26: 21–37, January 2014, www.plantcell.org ã 2014 American Society of Plant Biologists. All rights reserved. REVIEW The UV-B Photoreceptor UVR8: From Structure to Physiology Gareth I. Jenkins1 Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom Low doses of UV-B light (280 to 315 nm) elicit photomorphogenic responses in plants that modify biochemical composition, photosynthetic competence, morphogenesis, and defense. UV RESISTANCE LOCUS8 (UVR8) mediates photomorphogenic responses to UV-B by regulating transcription of a set of target genes. UVR8 differs from other known photoreceptors in that it uses specific Trp amino acids instead of a prosthetic chromophore for light absorption during UV-B photoreception. Absorption of UV-B dissociates the UVR8 dimer into monomers, initiating signal transduction through interaction with CONSTITUTIVELY PHOTOMORPHOGENIC1. However, much remains to be learned about the physiological role of UVR8 and its interaction with other signaling pathways, the molecular mechanism of UVR8 photoreception, how the UVR8 protein initiates signaling, how it is regulated, and how UVR8 regulates transcription of its target genes. INTRODUCTION below (Caldwell et al., 1983; Jordan 1996; Rozema et al., 1997; Frohnmeyer and Staiger, 2003; Jenkins, 2009). Damage caused Light is of paramount importance in promoting the growth and by UV-B exposure is ameliorated in several ways, in particular by development of plants. In addition to its role as the energy source antioxidant systems and enzymes that repair DNA damage. An for photosynthesis, light regulates numerous aspects of plant important feature of these protective responses is that they are form and function throughout the life cycle, from seedling es- stimulated when plants are exposed to UV-B.
    [Show full text]
  • Redistribution and Reduction of Interphotoreceptor Retinoid-Binding Protein During Ocular Coronavirus Infection
    Investigative Ophthalmology & Visual Science, Vol. 33, No. 1, January 1992 Copyright © Association for Research in Vision and Ophthalmology Redistribution and Reduction of Interphotoreceptor Retinoid-Binding Protein During Ocular Coronavirus Infection Suson G. Robbins,* Barbara Wiggert.f Geetha Kutty,f Gerald J. Chader.f Barbara Derrick,* and John J. Hooks'1 Inoculation of the neurotropic coronavirus mouse hepatitis virus strain JHM intravitreally or into the anterior chamber causes acute infection of the retinal pigment epithelium (RPE) and neural retina. Weeks later, many retinas have foci of moderate to severe atrophy. The effect of coronavirus infection (after intravitreal inoculation) was examined on interphotoreceptor retinoid-binding protein (IRBP), the glycolipoprotein in the interphotoreceptor matrix (IPM) thought to transport retinoids between the photoreceptors and the RPE. Changes in IRBP distribution accompanied virus-associated retinal pa- thology, including photoreceptor loss and RPE abnormalities. Immunohistochemistry on days 3 and 6 showed that IRBP had diffused into the neural retina away from the IPM. The IRBP became localized abnormally in the same areas as virus-induced lesions, shown by staining adjacent sections with a monoclonal antibody specific for the viral nucleocapsid protein. Moreover, the level of IRBP in isolated retinas, measured in an immunoslot-blot assay, decreased significantly by day 3 and remained low through day 23. This decrease was confirmed in eyecups isolated on day 6. It may be caused in part by loss of photoreceptors and diffusion of IRBP through the retina into the vitreous. These studies show that a virus may induce an acute, limited infection in the retina that can be cleared by the host.
    [Show full text]
  • Light Modulates Important Physiological Features of Ralstonia
    www.nature.com/scientificreports OPEN Light modulates important physiological features of Ralstonia pseudosolanacearum during the colonization of tomato plants Josefna Tano1,6, María Belén Ripa1,6, María Laura Tondo2, Analía Carrau1, Silvana Petrocelli2, María Victoria Rodriguez3, Virginia Ferreira4, María Inés Siri4, Laura Piskulic5 & Elena Graciela Orellano1* Ralstonia pseudosolanacearum GMI1000 (Rpso GMI1000) is a soil-borne vascular phytopathogen that infects host plants through the root system causing wilting disease in a wide range of agro- economic interest crops, producing economical losses. Several features contribute to the full bacterial virulence. In this work we study the participation of light, an important environmental factor, in the regulation of the physiological attributes and infectivity of Rpso GMI1000. In silico analysis of the Rpso genome revealed the presence of a Rsp0254 gene, which encodes a putative blue light LOV-type photoreceptor. We constructed a mutant strain of Rpso lacking the LOV protein and found that the loss of this protein and light, infuenced characteristics involved in the pathogenicity process such as motility, adhesion and the bioflms development, which allows the successful host plant colonization, rendering bacterial wilt. This protein could be involved in the adaptive responses to environmental changes. We demonstrated that light sensing and the LOV protein, would be used as a location signal in the host plant, to regulate the expression of several virulence factors, in a time and tissue dependent way. Consequently, bacteria could use an external signal and Rpsolov gene to know their location within plant tissue during the colonization process. Light is an important environmental factor in all ecosystems because it is a source of energy and information.
    [Show full text]
  • The Hiscl1 Histamine Receptor Acts in Photoreceptors to Synchronize Drosophila Behavioral Rhythms with Light-Dark Cycles
    ARTICLE https://doi.org/10.1038/s41467-018-08116-7 OPEN The HisCl1 histamine receptor acts in photoreceptors to synchronize Drosophila behavioral rhythms with light-dark cycles Faredin Alejevski1, Alexandra Saint-Charles1,2, Christine Michard-Vanhée1, Béatrice Martin1, Sonya Galant1, Daniel Vasiliauskas1 & François Rouyer 1 1234567890():,; In Drosophila, the clock that controls rest-activity rhythms synchronizes with light-dark cycles through either the blue-light sensitive cryptochrome (Cry) located in most clock neurons, or rhodopsin-expressing histaminergic photoreceptors. Here we show that, in the absence of Cry, each of the two histamine receptors Ort and HisCl1 contribute to entrain the clock whereas no entrainment occurs in the absence of the two receptors. In contrast to Ort, HisCl1 does not restore entrainment when expressed in the optic lobe interneurons. Indeed, HisCl1 is expressed in wild-type photoreceptors and entrainment is strongly impaired in flies with photoreceptors mutant for HisCl1. Rescuing HisCl1 expression in the Rh6-expressing pho- toreceptors restores entrainment but it does not in other photoreceptors, which send his- taminergic inputs to Rh6-expressing photoreceptors. Our results thus show that Rh6- expressing neurons contribute to circadian entrainment as both photoreceptors and inter- neurons, recalling the dual function of melanopsin-expressing ganglion cells in the mam- malian retina. 1 Institut des Neurosciences Paris-Saclay, Univ. Paris Sud, CNRS, Université Paris-Saclay, 91190 Gif-sur-Yvette, France. 2Present address: Institut de la Vision, Univ. P. & M. Curie, INSERM, CNRS, Sorbonne Université, Paris 75012, France. These authors contributed equally: Faredin Alejevski, Alexandra Saint-Charles. Correspondence and requests for materials should be addressed to F.R.
    [Show full text]
  • Structure of a LOV Protein in Apo-State and Implications for Construction of LOV-Based Optical Tools
    www.nature.com/scientificreports OPEN Structure of a LOV protein in apo-state and implications for construction of LOV-based optical Received: 19 October 2016 Accepted: 17 January 2017 tools Published: 17 February 2017 Vladimir Arinkin1,*, Joachim Granzin1,*, Katrin Röllen1,†, Ulrich Krauss2, Karl-Erich Jaeger2,3, Dieter Willbold1,4 & Renu Batra-Safferling1 Unique features of Light-Oxygen-Voltage (LOV) proteins like relatively small size (~12–19 kDa), inherent modularity, highly-tunable photocycle and oxygen-independent fluorescence have lately been exploited for the generation of optical tools. Structures of LOV domains reported so far contain a flavin chromophore per protein molecule. Here we report two new findings on the short LOV protein W619_1- LOV from Pseudomonas putida. First, the apo-state crystal structure of W619_1-LOV at 2.5 Å resolution reveals conformational rearrangements in the secondary structure elements lining the chromophore pocket including elongation of the Fα helix, shortening of the Eα-Fα loop and partial unfolding of the Eα helix. Second, the apo W619_1-LOV protein binds both natural and structurally modified flavin chromophores. Remarkably different photophysical and photochemical properties of W619_1-LOV bound to 7-methyl-8-chloro-riboflavin (8-Cl-RF) and lumichrome imply application of these variants as novel optical tools as they offer advantages such as no adduct state formation, and a broader choice of wavelengths for in vitro studies. Light-oxygen-voltage (LOV) flavoproteins belong to the Per-ARNT-Sim (PAS) domain superfamily sharing the canonical PAS protein fold1,2. Widely distributed in multiple kingdoms of life3–5, LOV proteins control a num- ber of cellular responses like phototropism, chloroplast movement, stomatal opening, regulation of circadian rhythms, photo-induced growth patterns and pigment synthesis6–8.
    [Show full text]
  • Two Rhodopsins Mediate Phototaxis to Low- and High-Intensity Light in Chlamydomonas Reinhardtii
    Two rhodopsins mediate phototaxis to low- and high-intensity light in Chlamydomonas reinhardtii Oleg A. Sineshchekov*†‡, Kwang-Hwan Jung*‡, and John L. Spudich*§¶ *Department of Microbiology and Molecular Genetics, and §Center for Membrane Biology, University of Texas Medical School, Houston, TX 77030; and †Department of Biology, Moscow State University, Moscow 119899, Russia Communicated by Winslow R. Briggs, Carnegie Institution of Washington, Stanford, CA, April 23, 2002 (received for review March 22, 2002) We demonstrate that two rhodopsins, identified from cDNA se- Photoreceptor current generation is the earliest detected conse- quences, function as low- and high-light-intensity phototaxis recep- quence of light absorption by the phototaxis-receptor molecules, tors in the eukaryotic alga Chlamydomonas reinhardtii. Each of the occurring Ͻ3 ␮s after a laser flash (9, 13). The localization of the receptors consists of an Ϸ300-residue seven-transmembrane helix current to the eyespot region of the cell corresponds to the expected domain with a retinal-binding pocket homologous to that of archaeal location of the pigments (10, 11), and its action spectrum measured rhodopsins, followed by Ϸ400 residues of additional membrane- in vivo matches that of phototaxis (8) and of the photophobic associated portion. The function of the two rhodopsins, Chlamydo- response (14). The sensitivity of the current to inhibitors (8, 10, 11) monas sensory rhodopsins A and B (CSRA and CSRB), as phototaxis and its chromophore requirements studied in retinal-deficient receptors is demonstrated by in vivo analysis of photoreceptor elec- mutants (15) confirm its role in photomovement. Thus, the pho- trical currents and motility responses in transformants with RNA toreceptor current provides a direct probe for activity of the interference (RNAi) directed against each of the rhodopsin genes.
    [Show full text]
  • Homologs of Vertebrate Opn3 Potentially Serve As a Light Sensor in Nonphotoreceptive Tissue
    Homologs of vertebrate Opn3 potentially serve as a light sensor in nonphotoreceptive tissue Mitsumasa Koyanagi1, Eiichiro Takada1, Takashi Nagata, Hisao Tsukamoto, and Akihisa Terakita2 Department of Biology and Geosciences, Graduate School of Science, Osaka City University, Osaka 558-8585, Japan Edited by King-Wai Yau, The Johns Hopkins School of Medicine, Baltimore, MD, and approved February 15, 2013 (received for review November 7, 2012) Most opsins selectively bind 11-cis retinal as a chromophore to opsins, the members of the retinochrome and peropsin groups form a photosensitive pigment, which underlies various physiolog- preferentially bind all-trans retinal, and light absorption causes ical functions, such as vision and circadian photoentrainment. Re- all-trans to 11-cis isomerization (8, 11–13). Therefore, the mem- cently, opsin 3 (Opn3), originally called encephalopsin or panopsin, bers of these two groups are considered to be retinal photo- and its homologs were identified in various tissues including brain, isomerases that produce 11-cis retinal. Collectively, opsins from eye, and liver in both vertebrates and invertebrates, including hu- seven of the eight phylogenetic groups have been characterized man. Because Opn3s are mainly expressed in tissues that are not to date. considered to contain sufficient amounts of 11-cis retinal to form The Opn3 group is the final distinct group, containing mam- pigments, the photopigment formation ability of Opn3 has been malian ospin 3 (Opn3), originally called encephalopsin or pan- of interest. Here, we report the successful expression of Opn3 opsin, teleost multiple tissue (TMT) opsin, insect pteropsin, and homologs, pufferfish teleost multiple tissue opsin (PufTMT) and annelid c-opsin (14–17).
    [Show full text]
  • Exaptations.Pdf
    Prospects & Overviews Problems & Paradigms How exaptations facilitated photosensory evolution: Seeing the light by accident Gregory S. Gavelis1)2)Ã, Patrick J. Keeling2) and Brian S. Leander2) Exaptations are adaptations that have undergone a major zone, as well as dark ecosystems illuminated by biolumines- change in function. By recruiting genes from sources cence [1, 2]. The selective advantages of exploiting this information have resulted in a great diversity of photoreceptive originally unrelated to vision, exaptation has allowed for systems (Fig. 1). Eyes (or eyespots) in animals and some protists sudden and critical photosensory innovations, such as are extraordinarily complex, and how this complexity evolved lenses, photopigments, and photoreceptors. Here we has been a longstanding question [3]. It is clear that visual review new or neglected findings, with an emphasis on systems have become superbly suited to their tasks through the unicellular eukaryotes (protists), to illustrate how exapta- gradual refinement of pre-existing features such as photo- receptors, photopigments, and lenses. But how did these tion has shaped photoreception across the tree of life. features acquire photosensory roles in the first place? Protist phylogeny attests to multiple origins of photore- Gould and Vrba coined the term “exaptation” to describe ception, as well as the extreme creativity of evolution. By traits that became used for different functions than those for appropriating genes and even entire organelles from which they had originally evolved [4]. This concept is useful foreign organisms via lateral gene transfer and endo- to explain the evolution of some important features. For symbiosis, protists have cobbled photoreceptors and instance, the feathers of Archaeopteryx were originally adapted for warmth, but through exaptation, they became eyespots from a diverse set of ingredients.
    [Show full text]
  • UV-Sensitive Photoreceptor Protein OPN5 in Humans and Mice
    UV-Sensitive Photoreceptor Protein OPN5 in Humans and Mice Daisuke Kojima1,2*., Suguru Mori1., Masaki Torii1., Akimori Wada3, Rika Morishita4, Yoshitaka Fukada1* 1 Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan, 2 Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Kawaguchi, Saitama, Japan, 3 Department of Organic Chemistry for Life Science, Kobe Pharmaceutical University, Kobe, Hyogo, Japan, 4 Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan Abstract A variety of animal species utilize the ultraviolet (UV) component of sunlight as their environmental cues, whereas physiological roles of UV photoreception in mammals, especially in human beings, remain open questions. Here we report that mouse neuropsin (OPN5) encoded by the Opn5 gene exhibited an absorption maximum (lmax) at 380 nm when reconstituted with 11-cis-retinal. Upon UV-light illumination, OPN5 was converted to a blue-absorbing photoproduct (lmax 470 nm), which was stable in the dark and reverted to the UV-absorbing state by the subsequent orange light illumination, indicating its bistable nature. Human OPN5 also had an absorption maximum at 380 nm with spectral properties similar to mouse OPN5, revealing that OPN5 is the first and hitherto unknown human opsin with peak sensitivity in the UV region. OPN5 was capable of activating heterotrimeric G protein Gi in a UV-dependent manner. Immuno-blotting analyses of mouse tissue extracts identified the retina, the brain and, unexpectedly, the outer ears as the major sites of OPN5 expression. In the tissue sections of mice, OPN5 immuno-reactivities were detected in a subset of non-rod/non-cone retinal neurons as well as in the epidermal and muscle cells of the outer ears.
    [Show full text]
  • Electronic and Spatial Characteristics of the Retinylidene Chromophore of Rhodopsin
    Electronic and spatial characteristics of the retinylidene chromophore in rhodopsin Verhoeven, M.A. Citation Verhoeven, M. A. (2005, November 15). Electronic and spatial characteristics of the retinylidene chromophore in rhodopsin. Leiden Institute of Chemistry, Biophysical Organic Chemistry/Solid-state NMR, Faculty of Science, Leiden University. Retrieved from https://hdl.handle.net/1887/12041 Version: Corrected Publisher’s Version Licence agreement concerning inclusion of doctoral thesis in the License: Institutional Repository of the University of Leiden Downloaded from: https://hdl.handle.net/1887/12041 Note: To cite this publication please use the final published version (if applicable). Electronic and Spatial Characteristics of the Retinylidene Chromophore of Rhodopsin PROEFSCHRIFT ter verkrijging van de graad van Doctor aan de Universiteit Leiden, op gezag van de Rector Magnificus Dr. D.D. Breimer, hoogleraar in de faculteit der Wiskunde en Natuurwetenschappen en die der Geneeskunde, volgens besluit van het College voor Promoties te verdedigen op dinsdag 15 november 2005 klokke 14.15 uur door Michiel Adriaan VERHOEVEN geboren te Malden in 1972 Promotiecommissie Promotores: Prof. dr. H.J.M. de Groot Prof. dr. W.J. de Grip Referent: Prof. dr. J. Reedijk Overige leden: Prof. dr. L.W. Jenneskens Prof. dr. A.P. IJzerman Prof. dr. H.S. Overkleeft Prof. dr. J. Brouwer Table of contents CHAPTER 1 GENERAL INTRODUCTION .......................................................................................................9 1.1 INTRODUCTION
    [Show full text]